Techniques for ultrasound imaging various parts of the body are well known. An ultrasonic scanner is placed on the body surface overlying the area to be imaged. The sound waves generated by the scanner are directed toward the area to be imaged. The scanner then detects sound waves reflected from the underlying area and translates the signal into images.
The acoustic properties of a substance, such as an organ system, will depend upon the velocity of the ultrasonic transmissions and the density of the substance. Changes in the substance's acoustic properties will be most prominent at the interface of components of the substance differing in density, such as solid, liquid, and gas components. When ultrasonic energy is transmitted through a substance, the changes in acoustic properties (e.g., density) of the substance cause changes in the reflection characteristics, resulting in a more intense sound reflection signal received by the ultrasonic scanner.
Ultrasound contrast agents are introduced into the body organ system being imaged using ultrasound, and there act to influence the ultrasound signal in a way that enhances the ultrasound image. The contrast agent may be ingested or injected into and perfuse the microvasculature of the tissue desired to be imaged, to provide clearer images of the tissue. Such ultrasound contrast agents may be useful in helping to diagnose diseases earlier and more accurately.
Liquid and solid contrast agents containing entrapped gas are known in the art. The microbubbles provided by these contrast agents act as sound wave reflectors because of the acoustic differences between the gas microbubble and surrounding liquid.
Feinstein, U.S. Pat. No. 4,572,203, issued Feb. 25, 1986 discloses "microbubbles" of about 6-20 microns diameter produced by sonication of certain viscous solutions, as ultrasound contrast agents. Feinstein, U.S. Pat. No. 4,572,203, issued Feb. 25, 1986 also discloses solid or semi-solid metal-containing microparticles, such as glass or graphite, not containing trapped air, small enough to pass through capillaries, as ultrasound contrast agents. Also disclosed are microspheres formed from an amino acid polymer matrix, such as albumin, with magnetic particles, such as magnetite (Fe.sub.3 O.sub.4) embedded therein.
Tickner, U.S. Pat. No. 4,265,251, issued May 5, 1981 discloses the use of certain saccharide composition "microbubble" particles with a hollow gas-filled interior space as ultrasound enhancing agents.
Rasor and Tickner, U.S. Pat. No. 4,442,843, issued Apr. 17, 1984, U.S. Pat. No. 4,657,756, issued Apr. 14, 1987, and U.S. Pat. No. 4,681,119, issued Jul. 21, 1987, to Schering, disclose aggregates of microparticles (of 1-50 micron diameter) of a solid material, which are soluble in blood, containing gas in the voids between the particles, or with gas adsorbed on the surface of the particle, or containing gas as an integral part of the internal structure of the particle, for use in ultrasound imaging. The following solid materials are disclosed: various saccharides, NaCl, sodium citrate, sodium acetate, sodium tartrate, CaCl.sub.2 and AlCl.sub.3.
Hilmann et al., European Patent Application Publication Number 122,624, to Schering, published Oct. 24, 1984 discloses microparticles comprised of a solid surface-active substance, including various organic lipophilic compounds, with enclosed air, as ultrasound contrast agents. Also dislosed is the combination of particles of the surface-active material and particles of a non-surface active material, such as sodium chloride, sodium citrate, sodium acetate, sodium tartrate, and various saccharides.